End Of Treatment Period Research Articles

P4394Two-year therapeutic effectiveness of pharmacotherapy versus electronic cigarettes for smoking cessation: A single-center experience

Abstract Purpose Aim of this study is to compare the long-term (2-year) effectiveness of e-cigarettes (EC) vs pharmacotherapy for smoking cessation. Methods We analyzed data from 173 smokers visiting our unit from January 2012 to December 2016 followed for two years. Of them, 128 were treated with varenicline for 3 months and 45 used EC for 3 months to quit smoking. Results There were not significant differences in severity of nicotine dependence and cigarette consumption (pack-years) between the two groups. Compared to smokers under varenicline therapy, EC users were younger (38±7 vs 49±12 years, P<0.01). The two groups had no gender difference and similar prevalence of traditional risk factors and coronary artery disease. Figure shows the smoking abstinence rates at the end of treatment period (3 months) and the continuous abstinence rates at 2 years. At the end of treatment period, 79 (62%) of subjects under therapy with varenicline were abstinent from smoking while 31 (69%) of individuals using EC did not smoke combustile cigarettes 3 months after the initiation of vaping. The continuous abstinence rates at 2 years was significantly higher among individuals treated with varenicline compared to EC (41% vs 24%, P<0.05). Interestingly, at 2 years, 12 EC users (27%) continued vaping alone and 21 (47%) were dual (EC and tobacco cigarette) users. EC vs varenicline and smoking abstinence Conclusions Our preliminary data indicate that smokers who received varenicline had significantly higher continuous abstinence rates compared to individuals who used EC at a 2-year follow-up. Furthermore, almost half of the later group maintained dual use.

1733TiP - A pilot study of oral paclitaxel (ORAXOL) in subjects with cutaneous angiosarcomas (KX-ORAX-010)

BackgroundAngiosarcomas (AS) are rare and aggressive tumors of endothelial cell origin. About half of patients present with a primary cutaneous lesion, most commonly over the scalp. Intravenous (IV) weekly paclitaxel (Pac) is the current accepted standard-of-care in inoperable or progressive disease. Median PFS is 3.8 months. IV Pac is associated with dose-limited toxicities including peripheral neuropathy, development of infusional reactions and anaphylaxis, in part due to the Cremophor EL formulation vehicle. Pac is a P-glycoprotein (P-gp) substrate. Pac is a substrate for the Pgp pump in the intestinal cells which leads to efflux of Pac back into the intestinal lumen, thereby making the drug nonbioavailable when taken orally. ORAXOL is a combination product of 2 separate drugs; oral Pac and a novel Pglycoprotein (Pgp) inhibitor, HM30181 methanesulfonate monohydrate (HM30181A). This allows for intestinal absorption and systemic exposure of Pac. ORAXOL has been studied in bioavailability and bioequivalence studies confirming its safety profile. A multi-center phase III study comparing ORAXOL and IV Pac in women with metastatic breast cancer is on-going. We are currently recruiting patients on a multi-center pilot study to determine the efficacy of ORAXOL in cutaneous AS. Trial designThis is a multi-center, international, open-label, pilot study to evaluate the activity, safety, and tolerability of ORAXOL in subjects with cutaneous AS who have not been treated previously with taxanes. ORAXOL (15mg oral HM30181A & 205mg/m2 oral Pac) will be administered once daily for 3 consecutive days every week from Weeks 1 through 25; HM30181A is administered 1hour before oral Pac on dosing days. Subjects who do not have disease progression at the end of treatment period are eligible to continue ORAXOL in the treatment extension phase. Primary objective is to determine the response rate (RR) within 6 months of initiation of treatment. Secondary objectives include (i) safety and tolerability, (ii) PFS and (iii) OS, (iv) duration of- and (v) time to-best response. Up to 25 evaluable subjects across 4 study sites will be enrolled in this study. The first patient has started dosing in December 2018. Clinical trial identificationNCT03544567. Legal entity responsible for the studyAthenex Inc. FundingAthenex Inc. DisclosureM.R. Kwan: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. D. Cutler: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. D. Kramer: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. W. Chan: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. All other authors have declared no conflicts of interest.

Evaluation of the Effects of Low-Level Laser Therapy on Diabetic Bone Healing.

The aim of the present study was to evaluate the effects of low-level laser therapy (LLLT) and biphasic alloplastic bone graft material on diabetic bone healing. Induction of diabetes was performed in 14 male Sprague-Dawley rats by intraperitoneal injection of a 50 mg/kg dose of streptozotocin. Two bilaterally symmetrical non-critical-sized bone defects were created in the parietal bones in each rat. Right defects were filled with biphasic alloplastic bone graft. Rats were randomly divided into 2 groups, with 1 group receiving 10 sessions of LLLT (GaAlAs, 78.5 J/cm, 100mW, 0.028 cm beam). The LLLT was started immediately after surgery and once every 3 days during postoperative period. At the end of treatment period, new bone formation and osteoblast density were determined using histomorphometry. Empty (control), graft-filled, LLLT-treated and both graft-filled and LLLT-treated bone defects were compared. New bone formation was higher in the graft treatment samples compared with the control (P = 0.009) and laser samples (P = 0.029). In addition, graft-laser combination treatment samples revealed higher bone formation than control (P = 0.008) and laser (P = 0.026) samples. Osteoblast density was significantly higher in the laser treatment (P <0.001), graft treatment (P = 0.001) and graft-laser combination treatment (P <0.001) samples than control samples. In addition, significantly higher osteoblast density was observed in the graft-laser combination treatment samples compared to the graft treatment samples (P = 0.005). The LLLT was effective to stimulate osteoblastogenesis but failed to increase bone formation. Graft augmentation for treatment of bone defects seems essential for proper bone healing in diabetes, regeneration may be supported by the LLLT to enhance osteoblastogenesis.

Antioxidant activity of dichloromethane fraction of Dichrocephala integrifolia in Salmonella typhi-infected rats

ObjectiveInfectious diseases such as typhoid fever lead to the formation of free radicals which can damage the body. Many medicinal plants have antioxidant molecules that neutralize free radicals. The present work evaluated the antioxidant activity and histopathological effects of the dichloromethane fraction of Dichrocephala integrifolia in Salmonella typhi-infected rats. MethodsThe S. typhi-infected rats concurrently received daily doses of D. integrifolia extract at doses of 25, 50 and 100 mg/kg body weight or ciprofloxacin (5 mg/kg body weight) for 15 days. Body temperature was measured daily during infection and treatment periods. At the end of treatment period, the animals were sacrificed and biological responses including hematological parameters, superoxide dismutase and catalase activities, and glutathione, malondialdehyde and nitric oxide concentrations were evaluated. ResultsThe elevated body temperature induced by infection was significantly decreased in animals treated with 25, 50 or 100 mg/kg of the extract. Platelet levels decreased slightly in infected rats, while treatment with the dichloromethane fraction of D. integrifolia significantly increased platelet levels; this response was greater than that elicited by ciprofloxacin. The doses of 50 and 100 mg/kg of the dichloromethane fraction of D. integrifolia notably decreased monocyte and neutrophil values. Activity of superoxide dismutase and catalase and levels of glutathione in the tissues of treated animals were increased significantly (P < 0.01), while malondialdehyde and nitric oxide levels were significantly decreased (P < 0.01), following treatment with the dichloromethane fraction of D. integrifolia. ConclusionThe results of this study show that the dichloromethane fraction of D. integrifolia has protective effects against a series of pathological conditions initiated by oxidation and tissue damage in the course of a S. typhi infection.

The role of melatonin supplement in metabolic syndrome

PurposeMetabolic syndrome contains metabolic disorders that have association with other chronic diseases. Melatonin is a bioactive compound which is found in plants and also produced in the body. The purpose of this paper is to assess the effect of melatonin supplement on metabolic syndrome components, also leptin and adiponectin blood concentrations in patients with metabolic syndrome.Design/methodology/approachA double blind, placebo-controlled, randomized clinical trial was conducted on 70 subjects with metabolic syndrome. Participants received 6 mg/day melatonin or placebo before bedtime for 12 weeks. At the beginning and end of treatment period, blood samples were collected and biochemical parameters were measured. In addition, blood pressure and anthropometric indices were examined before and after the supplementation. Independent samplet-test was used to compare changes in metabolic syndrome components between the two study groups.FindingsResults showed a significant reduction in waist circumference (−1.54 vs −0.04 cm;p= 0.036), systolic blood pressure (−3.52 vs 0.79 mmHg;p= 0.020), diastolic blood pressure (−1.50 vs 1.73 mmHg;p= 0.014), serum leptin concentration (−2.54 vs 0.27ng/ml;p= 0.041) and an elevation in high-density lipoprotein cholesterol (2.19 vs −0.79 mg/dl;p= 0.038) in the melatonin group compared to the placebo.Research limitations/implicationsIf insulin concentration had been measured, it might have revealed better interpretation of melatonin effect on fasting blood glucose.Originality/valueThis study showed that melatonin as a nutritional supplement improved most metabolic syndrome components and concentration of leptin in the melatonin group compared to the placebo.

The Effect of Cerium Oxide During Pregnancy on the Development of the Testicular Tissue of Newborn NMRI Mice.

Cerium(IV) oxide is widely used as a catalyst in all aspects of human life and human beings are exposed to these materials. The purpose of this experimental study was to investigate the effect of CeO2 during pregnancy on alterations in the testis tissue and blood biochemical parameters in newborn mice. Pregnant NMRI mice were divided randomly into five groups (n = 6 for each group) including one control group and 4 treatment groups. Injection of CeO2 solution was administered intraperitoneally at the doses of 10, 25, 80, and 250mg/kg.bw, respectively, on GD 7 and GD 14. At the end of treatment period, the testicular histological and biochemical parameters of 2- and 6-day-old newborns were analyzed, as well as the biochemical parameters in serum samples of 15-day-old newborns. The number of spermatogonia, Sertoli, and Leydig cells in the testis of the 2-day-old newborn and spermatogonia and Leydig cells in the testis of the 6-day-old newborns in the 250mg/kg.bw CeO2 treatment group was significantly reduced compared with the control group (P < 0.05). Testis MDA of the 2- and 6-day-old newborns in the treated group receiving 250mg/kg.bw of CeO2 was significantly higher than the control group (P < 0.001). There was no significant difference between serum MDA and TAC levels between the treated groups with different doses of CeO2 compared with the control group. Therefore, CeO2 given to dams during pregnancy may affect the testicular tissue and blood biochemical parameters in neonates and may be dose-dependent.

Bacillus clausii as adjunctive treatment for acute community-acquired diarrhea among Filipino children: a large-scale, multicenter, open-label study (CODDLE)

BackgroundDiarrhea is among the main causes of pediatric mortality in the Philippines. Probiotics have been shown to be beneficial in the management of acute diarrhea. Accordingly, the aim of this population-based study was to assess the safety and effectiveness of Bacillus clausii as an adjunct to standard therapy in Filipino children with acute community-acquired diarrhea of viral origin or associated with antibiotic administration.MethodsA total of 3178 patients (median age of 2 years) were enrolled in this open-label, multicenter, observational study, and were treated with one to two vials of Bacillus clausii in the following bacterial stains: O/C, SIN, N/R, and T (oral suspension of 2 billion spores per 5-mL vial) for 5 to 7 days. Diarrhea duration, number of stools per day, improvement in gastrointestinal symptoms, children’s overall acceptability of Bacillus clausii therapy, and safety and tolerability were assessed. Concomitant treatment with oral rehydration solutions (26.6%), zinc (23.9%), and antibiotics prescribed for conditions other than diarrhea (13.6%) was recorded during the study. All other probiotics and antidiarrheals were prohibited.ResultsTherapy with Bacillus clausii was well-tolerated, and the adverse event rate was very low (0.09%). All reported adverse events, which included vomiting, erythematous rashes and stool color change, were mild to moderate. In more than half of the per-protocol population (1535/2916; 52.6%), diarrhea was resolved within the first 3 days of treatment with Bacillus clausii. There was no significant difference (p = 0.297) in mean diarrhea duration between patients with either antibiotic-associated (3.3 ± 1.3 days) or viral diarrhea (3.4 ± 1.3 days). However, children who only received Bacillus clausii supplementation without zinc had a significantly shorter diarrhea duration (3.3 ± 1.3 days) compared to zinc-treated children (3.6 ± 1.6 days; p < 0.001). Bacillus clausii significantly reduced the mean number of stools per day, from 5.2 ± 2.0 stools at baseline to 1.2 ± 0.6 stools at study end (p < 0.001). Similarly, the proportion of patients with loose stools decreased from 81.6% at baseline to 9.2% at end of treatment period. Acceptability of Bacillus clausii therapy was high.ConclusionThis study adds knowledge on the good safety profile and on the effectiveness of Bacillus clausii as an adjunct treatment for acute childhood diarrhea.

Methodology of an exercise intervention program using social incentives and gamification for obese children

BackgroundTraditional exercise [supervised exercise (SE)] intervention has been proved to be one of the most effective ways to improve metabolic health. However, most exercise interventions were on a high-cost and small scale, moreover lacking of the long-term effect due to low engagement. On the other hand, it was noteworthy that gamification and social incentives were promising strategies to increase engagement and sustain exercise interventions effects; as well as mobile technologies such as WeChat also can provide an appropriate platform to deploy interventions on a broader, low-cost scale. Thus, we aim to develop a novel exercise intervention (‘S&G exercise intervention’) that combines SE intervention with gamification and social incentives design through WeChat, with the aim of improving metabolic health and poor behaviors among overweight and obesity children.MethodsWe propose a randomized controlled trial of a ‘S&G exercise intervention’ among 420 overweight and obese children who have at least one marker of metabolic syndrome. Children will be randomized to control or intervention group in a 1:1 ratio. The exercise intervention package includes intervention designs based on integrated social incentives and gamification theory, involving targeted essential volume and intensity of activity (skipping rope) as well as monitoring daily information and providing health advice by WeChat. Participants will undertake assessments at baseline, at end of intervention period, in the follow-up time at months 3,6,12. The primary outcome is outcome of metabolic health. Secondary outcomes include behavioral (e.g., diary physical activity, diet) and anthropometric measures (e.g., body fat rate and muscle mass).DiscussionsThis will be the first study to design an exercise intervention model that combines traditional supervised exercise (SE) intervention with gamification and social incentives theory through WeChat. We believed that this study could explore a low-cost, easy-to-popularize, and effective exercise intervention model for improving metabolic health and promote healthy among obese children. Furthermore, it will also provide important evidence for guidelines to prevent and improve metabolic health and health behaviors.Trial registration10-04-2019;Registration number: ChiCTR1900022396.

Mexican population sub-analysis of the lixilan clinical program with the fixed ratio combination of insulin glargine and lixisenatide (iGlarLixi)

AimTo evaluate the efficacy and safety of iGlarLixi in Mexican patients with type 2 diabetes who participated in the LixiLan clinical trials and compare results with the rest of the patients. MethodsData was collected for Mexican patients who participated in either of three studies: phase 2 trial LixiLan-POC, that compared iGlarLixi vs insulin glargine (iGlar) on inadequately controlled patients with metformin; phase 3 trial LixiLan-O, comparing iGlarLixi vs iGlar and lixisenatide on inadequately controlled patients with oral antidiabetic agents; and finally the phase 3 trial LixiLan-L, comparing iGlarLixi vs iGlar on inadequately controlled patients with basal insulin. The primary endpoint was the change in HbA1c from baseline to end of treatment. ResultsIn the Mexican population, treatment with iGlarLixi significantly improved HbA1c compared with each component alone achieving an average of 6.5%; (6.17%, 6.63% and 6.73% for the LixiLan-POC, O and L studies respectively) and an average HbA1c reduction from baseline of 1.6%, for the three studies at end of treatment period. ConclusionThe efficacy and safety profile of iGlarLixi demonstrate a fair or better composite endpoint of HbA1c without hypoglycemia and no weight gain compared to overall trial population, which could help improve Mexican patients' outcomes.

HEPATOPROTECTIVE EFFECT OF PERILLYL ALCOHOL (POH) ON HIGH-FAT DIET-LOW-DOSE STREPTOZOTOCIN-INDUCED TYPE 2 DIABETES IN EXPERIMENTAL RATS

Objective: The aim of the present study was to investigate the hepatoprotectivity effect of perillyl alcohol in high-fat diet (HFD)-low-dose streptozotocin (STZ)-induced diabetic rats.&#x0D; Methods: Diabetes was induced in male albino Wistar rats by 4 weeks diet manipulation followed by a low single intraperitoneal injection of STZ (35 mg/kg body weight). Perillyl alcohol was administered orally (50 mg/kg body weight and 100 mg/kg body weight) for 30 days. Glibenclamide was used as a standard drug and given orally 6 mg/kg body weight. At the end of treatment period, levels of alkaline phosphatase (ALP), aspartate transaminase (AST) alanine transaminase (ALT), and bilirubin and serum protein were measured in serum of experimental rats. Histopathological studies of liver were also done with microscope.&#x0D; Results: The levels of ALP, AST ALT, and bilirubin were increased significantly in HFD-STZ-induced diabetic rats. Perillyl alcohol-treated diabetic rats showed marked restoration in the activity of ALP, AST, ALT, and bilirubin when compared with diabetic control rats. Perillyl alcohol and glibenclamide drug-treated rats showed reversible tissue regeneration with prominent hepatocytes.&#x0D; Conclusion: The present results clearly indicate that the perillyl alcohol has a potent efficacy for hepatoprotective effect in HFD- low-dose STZ-induced diabetic rats.

SAT-554 Teprotumumab in Graves' Orbitopathy: Extended Outcome Analyses

Objective A multicenter, double-masked, randomized, placebo-controlled, phase two trial of 88 patients with active, moderate-to-severe Graves’ orbitopathy (GO) has demonstrated a significant and rapid response to teprotumumab, an insulin-like growth factor 1 receptor inhibitory monoclonal antibody, when compared with placebo after 24 weeks (N Engl J Med 2017; 376:1748). We now report extended primary and secondary outcome analyses. Methods Seven weeks after final dose of study medication (week 28), the primary and secondary endpoints were analyzed in teprotumumab intent-to-treat patients as compared with placebo to assess possible relapse. This included the primary composite endpoint of percentage patients with ≥2 points reduction in clinical activity score (CAS, seven-point scale) and a reduction of ≥2 mm in proptosis, secondary endpoints of proptosis, CAS, diplopia grade, specific GO quality of life questionnaire (GO-QoL), and exploratory analyses of clinical severity, all in the study (more severely affected) eye. Results Thirty-one of 42 (74%) teprotumumab- and six of 45 (13%) placebo- treated patients reached the primary outcome at treatment week 28 (p<0.001). Response was maintained from end of treatment period (week 24) in 93% of those teprotumumab-treated patients who responded. Proptosis response was similar to the primary outcome, with 55% of those receiving teprotumumab having a high response (≥3mm decrease). Gender, race, smoking or baseline proptosis values did not impact proptosis response. At week 28, 37/42 (88%) of those receiving teprotumumab and 27/45 (60%) getting placebo reached the CAS outcome (p=0.003). All individual CAS components were different from placebo (p≤0.04) except eyelid erythema (p=0.06). Assessment of CAS and severity of GO favored teprotumumab: chemosis (percent of patients ≥1 grade reduction; p=0.11), swelling of eyelid (percent of patients ≥1 grade reduction; p=0.01) and lid aperture (percent of patients ≥2 mm reduction; p=0.09). From baseline there was a reduction in constant diplopia (36% vs 9.5%) and increase in those with no diplopia (9.5% vs. 50%) in the teprotumumab group. At week 24, significantly more teprotumumab-receiving patients had improved by ≥one grade than placebo (62% vs. 22%, p<0.001). Improvement of diplopia grade remained significant at week 28 off drug. Overall GO-QoL was higher in those receiving teprotumumab than in patients getting placebo (p<0.001). Teprotumumab did not affect thyroid function, which was stable in both study groups through the treatment phase and follow-up. Conclusions Teprotumumab reduced the composite primary outcome of proptosis and CAS, as well as improved diplopia and GO-QoL significantly at seven weeks following study treatment discontinuation. This analysis also indicates that proptosis can serve as a primary and sensitive outcome for future trials of therapeutic response in GO.

Effect of saffron (stigma of Crocus sativus L.) aqueous extract on ethanol toxicity in rats: A biochemical, histopathological and molecular study

Ethnopharmacological relevanceSaffron (Crocus sativus L.) is considered in the Iranian traditional medicine because of many therapeutic properties such as sedative agent, strengthen the stomach and liver, improving the uterus disorders and infectious wounds. The detoxification of alcohol was one of the most important of saffron effects in ancient medicine. Aim of the studyIn the current research, the protective effects of saffron aqueous extract (Aq. Ext.) versus oxidative stress, apoptosis, inflammation, histopathological and biochemical abnormalities induced by ethanol were evaluated. Materials & methodsThe male Wistar rats were divided into seven groups consisted of 6 rats in control (distilled water), ethanol (5 g/kg - 50% v/v), Aq. Ext. (40, 80 and 160 mg/kg) plus ethanol, Aq. Ext. 80 and 160 mg/kg. Animals were treated for four weeks and at the end of treatment period, histopathological damages, biochemical markers, apoptosis, levels of MDA and GSH, TNF-α and IL-6 were evaluated. ResultsEthanol induced nephrotoxicity and hepatotoxicity as evidenced by histopathological damages and biochemical abnormalities. The level of MDA was significantly enhanced while GSH content was remarkably reduced in ethanol-treated rats, but protective groups restored them. Also, the levels of TNF-α and IL-6 were regulated by Aq. Ext. Furthermore, the effects of ethanol on histopathological and biochemical parameters were improved by Aq. Ext. The ethanol increased the expression of Bax/Bcl2 ratio, caspase-3, -8, and -9. Real-time PCR and western blot analysis proved that Aq. Ext. treatment inhibited apoptosis induced by ethanol through decreasing the Bax/Bcl2 ratio (mRNA and protein) and caspases-3, -8, and -9 levels in the kidney and liver. ConclusionThe results of this research demonstrated that Aq. Ext. could exert protective effects against ethanol toxicity in rat kidney and liver via antioxidant, anti-apoptosis, and anti-inflammatory effects.

App-technology to improve lifestyle behaviors among working adults - the Health Integrator study, a randomized controlled trial

BackgroundMobile health, mHealth is recognized as a strategy to improve lifestyle behaviors. Research targeting specific lifestyle behaviors has shown that interventions using smartphones can be effective. However, few studies have evaluated solutions with multicomponent interventions, tailoring the intervention to the specific needs of the participant using a combination of mHealth and conventional treatment. To accomplish this, we developed Health Integrator, an mHealth platform with services and offers in the areas of diet, physical activity, sleeping habits, stress, alcohol and tobacco use. In the system, the user selects an area of intervention together with a health coach and set weekly goals. This study protocol presents the design and methodology of the Health Integrator Study, a randomized controlled trial to promote improved lifestyle behaviors.MethodsA three-arm parallel randomized controlled trial (1:1:1) is conducted in the Stockholm County, Sweden. In total, 209 employees at a four different companies representing both white and blue collar workers, have been recruited.Participants are randomized to either a control group or to one of two intervention groups receiving a 3-month lifestyle behavior change program including either 1) use of Health Integrator and monthly health coaching sessions or 2) only Health Integrator.At baseline and follow-up after 3- and 6-months, all participants answer questionnaires assessing lifestyle behaviors and quality of life. At baseline and the 3-month follow-up (end of intervention period), weight, height, waist circumference and blood pressure are measured, and all participants wear an Actigraph accelerometer for 7 days to assess physical activity. Blood lipid profile and HbA1c are measured among all participants at baseline. If baseline measures fall outside the normal range, a second measurement is done after 3 months.DiscussionThe Health Integrator Intervention Study will evaluate if a personalized intervention combining mHealth and conventional programs for lifestyle change, with or without additional health coach sessions, can improve lifestyle behaviors and quality of life. Based on the results from this trial, Health Integrator can easily be implemented within a broad public.Trial registrationClinicalTrials.gov Identifier: NCT03579342. Retrospectively registered, first submitted May 8, 2018.

Promoting physical activity in children through family-based intervention: protocol of the \u201cActive 1\u2009+\u2009FUN\u201d randomized controlled trial

BackgroundPhysical activity (PA) is beneficial to people’s physical and psychological health. Physically active children are likely to become active adults; thus, active lifestyles should be promoted from childhood. Parents are crucial for shaping their children’s behaviors, but many lack the knowledge and skills to provide optimal support for PA. The “Active 1 + FUN” intervention was designed to enhance PA of the whole family, and improve parenting methods of both fathers and mothers.Methods“Active 1 + FUN” is a family-based intervention designed using the tenets of self-determination theory. The intervention was designed to help parents support their children’s basic psychological needs for competence (by providing informational feedback and optimal challenges), autonomy (by exploring a variety of activities and reducing controlling behaviors), and relatedness (by increasing co-PA between parents and child). The intervention components include interactive workshops, activity sessions, physical activity homework, activity planning consultations, easy sports equipment, and online materials. A randomized controlled trial will be conducted to evaluate the intervention. A target sample of 204 Primary three to five students (8 to 11 years) and their parents will be randomly allocated to the experimental group or a wait-list control group. The experimental group will receive a ten-session intervention which spans approximately six months. The control group will receive intervention one year later. Children’s accelerometer-based leisure-time physical activity (primary outcome) and secondary outcomes will be assessed at baseline, at end of intervention period (6 months after baseline), and at follow-up (12 months after baseline). Qualitative interviews will be conducted to determine effective intervention components from the perspective of children and parents. We hypothesize that the intervention will increase parents’ and children’s activity behaviors and that children will experience higher levels of needs satisfaction with regard to physical activity participation.DiscussionPhysical activity interventions often target children only, but ones that also involve parents may be more beneficial. The “Active 1 + FUN” intervention will be organized and delivered by trained trainers. Consequently, this intervention could be scaled to a larger number of Hong Kong schools in the future and could impact a wider population of schoolchildren.Trial registrationANZCTR ACTRN12618001524280. Registered 11 September 2018.

Elimination of rose viruses using microshoot tip tissue culture

Virus elimination therapy for roses is very challenging. Foundation Plant Services at the University of California, Davis provides virus-tested rose propagation material to the rose nursery industry in the United States. Before 1999, heat treatment of potted plants was used to eliminate viruses. Success was varied and often the plant died during the treatment or was still virus-infected at the end of treatment period. In 2007 we reported on successful elimination of Apple mosaic virus (ApMV) and Prunus necrotic ringspot virus (PNRSV) using microshoot tip culture for six cultivars. However, survival was low and was cultivar dependent. In the period 2013 to 2016, 35 rose cultivars were subjected to microshoot tip tissue culture therapy. Microshoot tips measuring <0.5 to 0.7 mm, consisting of the meristem dome plus several pairs of leaf primordia, were excised from actively growing vegetative shoots and cultured in aseptic conditions. Different media, growth factors and light intensity were trialed. To date the most promising medium is: Murashige and Skoog (MS) salts and vitamins with 3% sucrose, 2.5 µmol 6-benzyladeninepurine (BA) and 0.4 µmol indole-3-acetic acid (IAA). Rooting was ex vitro by transplanting shoots that were approximately 5 cm long into a sealed container of saturated perlite to keep humidity high. One or more plants survived from 20 cultivars of the 35 that were treated (56%). Overall percent survival averaged 3% and ranged from 0 to 22%, depending on cultivar. Preliminary testing by ELISA shows that ApMV was eliminated; plants were still infected with PNRSV. Further testing using qPCR and other methods and trials are ongoing.

Aprepitant in Anti-histamine-refractory Chronic Nodular Prurigo: A Multicentre, Randomized, Double-blind, Placebo-controlled, Cross-over, Phase-II trial (APREPRU)

The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossed-over to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. (DRKS00005594; EudraCT Number: 2013-001601-85).

Minthostachys verticillata essential oils as potential phytogenic additives and chemoprotective strategy on aflatoxin B1 toxicity

ABSTRACT The aim of the current study was to evaluate the protective effects of Minthostachys verticillata essential oil (Mv-EO) against aflatoxin B1-induced toxicity in Vero cells in vitro and in male rats. The cytotoxicity of AFB1 (0-30 µg/mL) and Mv-EO (0-500 µg/mL) was determined on Vero cells using the Neutral Red assays. The tested Mv-EO did not cause genotoxicity or cytotoxicity in vivo and was able to attenuate AFB1-caused cytotoxicity and genotoxicity. Animals were divided into four groups consisting of 5 (five) rats in each group: T1 basal feed (BF – negative control), T2 BF + Mv-EO [0.04%], T3 BF + AFB1 [100 µg/kg], T4 BF + food with AFB1 [100 µg/kg] + Mv-EO [0.04%]. Tissue samples were collected at the end of treatment period for genotoxic study and histological examination. Treatment with Mv-EO alone and even combined with AFB1 showed a significant improvement in the histomorphometry of intestinal villi, without alteration of productive parameters. Also, the micronucleus test demonstrated that Mv-EO reduced AFB1-induced DNA damage on bone marrow cells of male Wistar rats. This study demonstrated that Mv-EO could be used as protective against AFB1-induced cytotoxicity and genotoxicity, and as phytogenic feed additive.

Predictors of effectiveness of glucagon-like peptide-1 receptor agonist therapy in patients with type 2 diabetes and obesity.

Diabetes type 2 (CD2), which develops mainly against visceral obesity, is socially significant disease, reduction of losses from which is priority in development of modern medicine. Glucagon-like peptide-1 receptor agonists (aGPP-1) is one of few groups of antidiabetic drugs that allows to reduce not only glycemia, but also weight with CD2. Taking into account predictors of response to therapy will allow highest probability to reach targets while maintaining safety of treatment, optimize recommendations for appointment of aGPP-1 as much as possible. Aims: to assess dynamics of metabolic parameters, to determine predictors of reduction in blood glucose, body weight and other metabolic parameters in AGPP-1 therapy in patients with type 2 diabetes with body mass index (BMI) &gt;35 kg/m. Material and methods. Study involved 33 patients (10 men, 23 women) who had been treated with aGPP-1, planned period of observation for 24 weeks. Early termination ofparticipation of 3 patients (1 - due to development ofpancreatitis, 2 - due to lack of financial opportunity to purchase the drug). Accordingly, 30 patients (10 men, 20 women) were included in final analysis. Examination consisted of survey, physical examination with measurement of anthropometric, clinical parameters, filling questionnaires. Data were evaluated initially and after 24 weeks of treatment. Results. Study found that patients who achieved weight loss &gt; 5% initially had higher BMI (p = 0.028), lower GLP-1 (p = 0.036), had lower level of ghrelin after sample with standard breakfast (p = 0.022). There was trend (p = 0.071) to greater decrease in BMI in patients with restrictive type of eating behavior compared to patients who had mixed type. More pronounced decrease in glycemia was noted in patients who had higher fasting plasma glucose level at inclusion (p = 0.001). Dynamics of HbA1C was better in patients with initially higher GLP-1 (p = 0.016) and higher levels of glycemia (p = 0.001). Also, in examined patients, there was statistically significant decrease in level of triglycerides, blood pressure by end of treatment period. Conclusions. Results indicate that there are different predictors for weight loss, glycemia and blood pressure in aGPP-1 therapy. In addition to metabolic parameters, level of orexigenic and anorexigenic hormones and psycho-social characteristics ofpatients help to estimate expected effect of therapy for ARP1. When predictors are identified, predictors of weight loss and carbohydrate metabolism compensation should be studied separately. Identification of response predictors is necessary to optimize indications for prescribing this group of drugs with CD2.

A 12-week Baduanjin Qigong exercise improves symptoms of ankylosing spondylitis: A randomized controlled trial

Background and purposeTherapeutic exercises are considered effective treatments for ankylosing spondylitis(AS). Current study aimed to evaluate efficacy and safety of Baduanjin qigong, a traditional Chinese exercise, for treatment of AS in a pilot RCT setting. Materials and methodsA total of 60 patients were randomly assigned, at a 1:1 ratio, to receive a 12-week Baduanjin qigong training(exercise group) or maintain their current lifestyle(no-treatment group). As primary outcomes, Bath Ankylosing Spondylitis Disease Activity Index(BASDAI) and other AS symptoms were assessed at baseline and end of treatment period. ResultsA total of 46 patients completed the study. At the end of treatment period, although total BASDAI scores were not statistically different, reduced scores were observed in the exercise group, compared to no-treatment group, with respect to fatigue(P = 0.03), intensity(P = 0.04) and duration(P = 0.01) of morning stiffness; exercise group also exhibited higher patient global assessment scores(P = 0.04). ConclusionBaduanjin qigong exercise appeared to improve AS symptoms.

Effect of 2-methoxyethanol induction on mice (Mus musculus) liver, kidney and ovary

These research was design to evaluate the effect of 2-methoxyethanol (2-ME) injection to the number of damaged hepatocyte, renal tubule, and follicle. This study was designed as Completely Randomized Design experimental study. Animal model used was 2-3 months old 20 female mice strain Balb/C mice weighed at 25-30 g. Mice were divided into 4 treatment groups; N (normal control), G1 (given 200 mg/kg BW 2-ME), G2 (given 250 mg/kg BW 2-ME), and G3 (given 300 mg/kg BW 2-ME). 2-ME was administered intraperitoneally daily for 5 consecutive days. Liver, kidney, and ovarium were removed at the end of treatment period then processed into histological slides. Damage on hepatocyte, nephron, and follicle was evaluated from tissue sections. Data collected was analyzed statistically. Result showed that level of damage increased along with 2-ME dose given to mice. KP3 was found to have highest number of damaged cell in the three organs, followed by KP2, and KP1 had the lowest number of damaged cells compared to KN. Injection of 2-ME at various doses could induce damage on hepatocyte, renal tubule, and ovarian follicle.